SLIT2
slit guidance ligand 2, the group of MicroRNA protein coding host genes
Basic information
Region (hg38): 4:20251905-20620561
Previous symbols: [ "SLIL3" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (221 variants)
- not_specified (147 variants)
- SLIT2-related_disorder (47 variants)
- Congenital_anomaly_of_kidney_and_urinary_tract (3 variants)
- Inborn_genetic_diseases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLIT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004787.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 66 | 16 | 84 | |||
| missense | 204 | 11 | 217 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 0 | 207 | 77 | 16 |
Highest pathogenic variant AF is 0.0000035242688
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SLIT2 | protein_coding | protein_coding | ENST00000504154 | 37 | 367302 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 8.44e-9 | 125729 | 0 | 19 | 125748 | 0.0000756 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.10 | 687 | 860 | 0.799 | 0.0000476 | 10078 |
| Missense in Polyphen | 334 | 453.38 | 0.7367 | 5335 | ||
| Synonymous | -0.291 | 325 | 318 | 1.02 | 0.0000179 | 2815 |
| Loss of Function | 7.68 | 7 | 82.1 | 0.0852 | 0.00000425 | 1026 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000197 | 0.000191 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000124 | 0.000123 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000377 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal chord development may play a role in guiding commissural axons once they reached the floor plate by modulating the response to netrin. In vitro, silences the attractive effect of NTN1 but not its growth- stimulatory effect and silencing requires the formation of a ROBO1-DCC complex. May be implicated in spinal chord midline post- crossing axon repulsion. In vitro, only commissural axons that crossed the midline responded to SLIT2. In the developing visual system appears to function as repellent for retinal ganglion axons by providing a repulsion that directs these axons along their appropriate paths prior to, and after passage through, the optic chiasm. In vitro, collapses and repels retinal ganglion cell growth cones. Seems to play a role in branching and arborization of CNS sensory axons, and in neuronal cell migration. In vitro, Slit homolog 2 protein N-product, but not Slit homolog 2 protein C-product, repels olfactory bulb (OB) but not dorsal root ganglia (DRG) axons, induces OB growth cones collapse and induces branching of DRG axons. Seems to be involved in regulating leukocyte migration. {ECO:0000269|PubMed:10102268, ECO:0000269|PubMed:10864954, ECO:0000269|PubMed:10975526, ECO:0000269|PubMed:11239147, ECO:0000269|PubMed:11309622, ECO:0000269|PubMed:11404413}.;
- Pathway
- Axon guidance - Homo sapiens (human);Angiogenesis overview;Spinal Cord Injury;Olfactory bulb development and olfactory learning;Robo4 and VEGF Signaling Pathways Crosstalk;Developmental Biology;SLIT2:ROBO1 increases RHOA activity;Activation of RAC1;Regulation of commissural axon pathfinding by SLIT and ROBO;Inactivation of CDC42 and RAC1;Netrin-1 signaling;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Axon guidance;Role of ABL in ROBO-SLIT signaling;Glypican 1 network
(Consensus)
Recessive Scores
- pRec
- 0.218
Intolerance Scores
- loftool
- rvis_EVS
- -2.18
- rvis_percentile_EVS
- 1.4
Haploinsufficiency Scores
- pHI
- 0.254
- hipred
- Y
- hipred_score
- 0.790
- ghis
- 0.553
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.744
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Slit2
- Phenotype
- digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; endocrine/exocrine gland phenotype;
Zebrafish Information Network
- Gene name
- slit2
- Affected structure
- supraoptic tract
- Phenotype tag
- abnormal
- Phenotype quality
- process quality
Gene ontology
- Biological process
- ureteric bud development;negative regulation of protein phosphorylation;cell migration involved in sprouting angiogenesis;negative regulation of leukocyte chemotaxis;aortic valve morphogenesis;pulmonary valve morphogenesis;axon guidance;motor neuron axon guidance;negative regulation of lamellipodium assembly;negative regulation of endothelial cell migration;negative regulation of smooth muscle cell migration;chemorepulsion involved in embryonic olfactory bulb interneuron precursor migration;chemorepulsion involved in postnatal olfactory bulb interneuron migration;corticospinal neuron axon guidance through spinal cord;negative regulation of cell growth;negative regulation of cell migration;negative regulation of actin filament polymerization;retinal ganglion cell axon guidance;cellular response to hormone stimulus;negative regulation of GTPase activity;Roundabout signaling pathway;positive regulation of apoptotic process;negative regulation of vascular permeability;branching morphogenesis of an epithelial tube;axon extension involved in axon guidance;positive regulation of axonogenesis;negative chemotaxis;induction of negative chemotaxis;negative regulation of small GTPase mediated signal transduction;response to cortisol;ventricular septum morphogenesis;apoptotic process involved in luteolysis;negative regulation of chemokine-mediated signaling pathway;cellular response to heparin;negative regulation of smooth muscle cell chemotaxis;negative regulation of mononuclear cell migration;negative regulation of neutrophil chemotaxis;negative regulation of monocyte chemotaxis;negative regulation of retinal ganglion cell axon guidance;negative regulation of cellular response to growth factor stimulus
- Cellular component
- extracellular region;extracellular space;cytoplasm;plasma membrane;membrane;extracellular exosome
- Molecular function
- GTPase inhibitor activity;calcium ion binding;protein binding;heparin binding;identical protein binding;protein homodimerization activity;laminin-1 binding;proteoglycan binding;Roundabout binding